A unique post-translational modification of a single protein in all animal cells has been described for the first time in our laboratories. This modification involves the conversion of a peptide-bonded lysine residue to the unusual amino acid, hypusine by covalent linkage between the epsilon amino terminal of the lysine and a butylamine group derived from the polyamine, spermidine. This is the only specific biochemical reaction yet described for polyamines in intact cells which can be related to a particular biochemical function. The rate of formation of hypusine was found to be proportional to the rate of protein synthesis in human lymphocytes, although the unique protein in which it occurs is synthesized continuously at all levels of protein synthesis. We have shown that this unique protein is the translation initiation factor 4D (eIF-4D). We have purified this protein in large quantities from human erythrocytes, where it is one of the major non-hemoglobin proteins. The role of initiation factor, and therefore in control of protein synthesis is being studied. The function of this protein in erythrocytes, where no protein synthesis occurs, is also under investigation.